Memory Improvement Through Nicotine Dosing (MIND) Study

Purpose

The purpose of the study is to see if daily transdermal nicotine is able to produce a
significant cognitive, clinical and functional improvement in participants with MCI. Neuronal
nicotinic receptors have long been known to play a critical role in memory function in
preclinical studies, with nicotine improving attention, learning, and memory function.
The study will enroll 300 participants for a 2 year period. Participants will be randomized
(50:50) to either the transdermal nicotine, beginning at 7mg/day, and increasing to 21mg/day,
or placebo skin patch.

Condition

Mild Cognitive Impairment

Eligibility

Eligible Ages

Between 55 Years and 90 Years

Eligible Genders

All

Accepts Healthy Volunteers

No

Inclusion Criteria

Participant must have a subjective memory concern as reported by participant, study
partner, or clinician

• Memantine and cholinesterase inhibitors are allowable if stable for 12 weeks prior
to screen

8. Geriatric Depression Scale score of less than or equal to 14

9. Study Partner is available who has frequent contact with the participant (e.g. an
average of 10 hours per week or more), and can accompany the participant to most
visits to answer questions about the participant

11. Good general health with no additional diseases/disorders expected to interfere with
the study

12. Participant is not pregnant, lactating, or of childbearing potential (i.e. women must
be two years post-menopausal or surgically sterile)

13. Completed six grades of education or has a good work history

14. Must speak English fluently

Exclusion Criteria

Regular use of tobacco products within the past year, such as smoking (cigarettes,
pipes, cigars, etc.) or use of other nicotine products (chewing tobacco, e-cigarettes,
nicotine patches, gum, sprays, etc.).

Major depression, bipolar disorder as described in DSM-V within the past 1 year or
psychotic features, agitation or behavioral problems within 3 months, which could lead
to difficulty complying with the protocol

History of schizophrenia (DSM V criteria)

History of alcohol or substance abuse or dependence within the past 2 years (DSM V
criteria)

Clinically significant or unstable medical condition, including uncontrolled
hypertension, uncontrolled diabetes, or significant cardiac, pulmonary, renal,
hepatic, endocrine, or other systemic disease in the opinion of the Investigator, may
either put the participant at risk because of participation in the study, or influence
the results, or the participant's ability to participate in the study.

Has had a history within the last 5 years of a primary or recurrent malignant disease
with the exception of non-melanoma skin cancers, resected cutaneous squamous cell
carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ
prostate cancer with normal prostate-specific antigen post-treatment

Clinically significant abnormalities in B12 or TFTs (Thyroid Function Tests) that
might interfere with the study. A low B12 is exclusionary, unless the required
follow-up labs (homocysteine (HC) and methylmalonic acid (MMA)) indicate that it is
not physiologically significant.

Study Design

Arm Groups

Arm

Description

Assigned Intervention

ExperimentalNicotine Transdermal Patch

150 participants will wear nicotine transdermal patches during waking hours. Active dose will titrate up from 3.5mg to 21mg in the first 6 weeks of treatment, remain at 21mg for 22.5 months, and then taper down in the final month of treatment

Drug: Nicotine Transdermal Patch
21mg Nicotine transdermal patches worn during waking hours. Active dose will titrate up from 3.5mg to 21mg in the first 6 weeks of treatment, remain at 21mg for 22.5 months, and then taper down in the final month of treatment.